Investigations in various aspects of the genetic control of the immune response are being conducted, and involve the following systems. (a) A single gene at a locus designated Ir-2 controls the ability of inbred mice to produce antibodies to the Ea-1 erythrocyte alloantigens. The allele for nonresponsiveness is dominant, and it seems to function on the basis of cross-tolerance. (b) The susceptibility of inbred rats to experimental allergic encephalomyelitis is also determined genetically. A single dominant gene linked to the Ag-B histocompatibility locus controls susceptibility in the Lewis x BN combination, whereas a number of genes are involved in the DA x BN combination. (c) Genes which control the ability of inbred rats to respond in vitro to phytohemagglutinin (PHA) are being studied. A single gene for high responsiveness is being transferred from the Lewis strain to the BN genetic background. A selection experiment for high and low responsiveness to PHA is being initiated, and will utilize a genetically heterogeneous foundation colony.